A newly found mouse model for the research of human gastric cancer

Mice play an important role in cancer research, but like all other animal models of human disease, mice have their limitations. Especially for gastric cancer, mice have always been considered to be poor subjects because rodents rarely have spontaneous gastric cancer.

A study published in the Gut Journal has described, an international team led by the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) found a single lineage of laboratory mice was obtained as a useful model of the disease after observing the onset of gastric tumors develops in a high rate in mice without exposure to carcinogens or genetic engineering. Subsequent genetic analysis of mouse tumors revealed that modulating the inflammatory response of NFKB1 protein may be a key driver of the model and human cancer susceptibility.

This new mouse model for studying gastric cancer will serve as a preclinical model for the discovery of therapeutic drugs and the treatment of precise gastric cancer. This discovery opens a window for the urgent development of new treatment options for gastric cancer. 

The stomach is above the abdomen and below the ribs. The stomach produces acids and enzymes that break down food before it reaches the small intestine. Gastric carcinoma is a malignant tumor originating from gastric mucosal epithelium. Gastric cancer is the fifth most common cancer in the world.

Promising novel mouse lineages are derived from the larger Collaborative Cross (CC) mouse model, which has recently been bred to have a higher genetic diversity than past populations and is, therefore, more comparable to humans. To explore whether this diversity could identify new models of human cancer, the researchers conducted a one-year monitoring of hundreds of mice from different CC strains. They discovered that each mouse in a strain formed a tumor at the end of the observation period - the stomach and lymph are the most common types.

After genome-wide analysis determined that these mice carry DNA sequence variants of the NFKB1 gene region, they attempted to explore how these mutations translate into molecular irregularities that cause cancer. To do this, they collaborated with Susan Celniker, a biochemist at Berkeley Labs, who tested a series of genes expressed in the stomach tissue of cancer-prone CC strains and made them small. The genes expressed in the stomach tissue of the mice were compared. A total of 166 genes were expressed differently in mice susceptible to cancer. It is worth noting that the human form of these genes is also differentially expressed in human gastric cancer tissues.

As recent research emphasizes the critical role of inflammation in cancer development, the team focused on genes associated with the inflammatory process. Abnormal expression of 19 inflammatory gene clusters was found to be a hallmark feature of human and mouse gastric tumors. Researchers hope to conduct research aimed at transforming these findings into prevention strategies and therapies as soon as possible.